The project is structured to test the hypothesis that immunologically mature rhesus monkeys transplanted with a genetically-mismatched heterotopic heart allograft at a time when the recipient's immune systems have been rendered incompetent with myeloblative total body irradiation will develop specific and permanent tolerance to the allografts. The hypothesis is based on the clonal selection theory of Burnet, confirmed experimentally by Medawar, which states that immune-competent lymphocytes present during fetal life which are reactive with self-antigens are permanently inactivated or eliminated. Myeloablative total body irradiation followed by autologous marrow transplantation after lymphocyte depletion of the marrow is the method employed to recreate a fetal immune environment in immunologically mature animals. Much effort has been devoted to the development of a working irradiated-monkey model and lymphocyte depletion of bone marrow in preparation for the experiments. Nearly all difficulties with these methods have been overcome, and experimentation is to begin soon.